Do DNA Vaccines Induce Autoimmune Disease?

Abstract

This report examines whether plasmid DNA vaccines induce the production of anti-DNA or anti-muscle cell autoantibodies. A three-fold increase in the number of B cells secreting immunoglobulin G (IgG) anti-DNA autoantibodies was detected in BALB/c mice immunized and boosted with any of three DNA plasmids (p < 0.004). This correlated with a transient increase in serum anti-DNA autoantibody titers but was not associated with the development of glomerulonephritis or autoimmune disease. None of the DNA vaccines examined stimulated the production of anti-muscle cell autoantibodies or the development of myositis. The effect of DNA vaccines on the development of nascent autoimmunity in lupus-prone (NZB × NZW)F₁ mice was also examined. Repeated vaccination did not alter the onset or course of disease in these animals. These findings suggest that DNA vaccines neither initiate nor accelerate the development of systemic autoimmunity. This work examines the safety of DNA vaccines, focusing on their potential to induce or accelerate autoimmunity. Repeated DNA immunization of BALB/c mice elicited a significant increase in the number of B cells secreting IgG anti-DNA autoantibodies, but had only a modest effect on serum autoantibody levels. Intramuscular vaccination did not induce the production of anti-muscle cell autoantibodies nor did it increase immunoglobulin (Ig) or cytokine production in the muscle bed. Normal mice vaccinated multiple times and followed for 16 months developed neither clinical nor serologic manifestations of autoimmune disease. Similarly, neither the onset nor severity of disease in lupus-prone (NZB × NZW)F₁ mice (animals sensitive to the immunostimulatory effects of nucleic acids) was altered by DNA vaccination. We conclude that the administration of conventional DNA vaccines is not associated with the induction of unsafe autoimmune sequelae.